Given the anti-leukemia activity of single-agent Blinatumomab in a difficult-to-treat population with r/r ALL, another BiTE® antibody targeting CD33, AMG 330, was developed for its suitability as immunotherapy in AML. To simulate the natural setting of target and T cells in AML patients, a long-term culture system was developed that supports the growth of primary AML cells ex-vivo for up to 5 weeks. AMG 330 activated and expanded residual autologous T cells within primary AML patient samples and eliminated CD33+ blasts even at very low effector to target ratios. The functional relevance of CD33 expression levels was shown by faster lysis kinetics of CD33BRIGHT versus CD33DIM AML cell lines and primary AML cells in ex-vivo cytotoxicity assays. However, by extending the exposure time to AMG 330, potent anti-leukemic activity was observed in both CD33BRIGHT and CD33DIM cells. AMG 330 treated T cells were shown to up-regulate the activation markers CD25, PD-1, TIM3 and LAG3, which was partially reversible after complete target cell elimination

Clinical experience with Blinatumomab in ALL and ex-vivo activity of AMG 330 in primary AML samples supports further development of BiTE® antibodies for targeted T cell-mediated immunotherapy of patients with malignancies.

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